Quan JingJing, Li Yan, Shen Minxue, Lu Yao, Yuan Hong, Yi Bin, Chen Xiang, Huang Zhijun
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Environ Sci Pollut Res Int. 2023 Apr;30(18):52421-52432. doi: 10.1007/s11356-023-25909-6. Epub 2023 Feb 25.
Previous studies have indicated that exposure to a single toxic metal can cause renal tubular damage, while evidence about the effects of multimetal exposure on renal tubular damage is relatively limited. We aimed to evaluate the relationships of multimetal coexposure with renal tubular damage in adults in heavy metal-polluted rural regions of China. A cross-sectional study of 1918 adults in China's heavy metal-contaminated rural regions was conducted. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the plasma levels of 18 metals in participants, and immune turbidimetry was used to measure sensitive biological indicators, reflecting renal tubular damage (including retinol-binding protein and β2-microglobulin). Least absolute shrinkage and selection operator (LASSO) penalized regression analysis, logistic and linear regression analysis, restricted cubic spline (RCS) regression analysis and the Bayesian kernel machine regression (BKMR) method were used to explore associations of multimetal coexposure with renal tubular damage risk or renal tubular damage indicators. Plasma selenium, cadmium, arsenic, and iron were identified as the main plasma metals associated with renal tubular damage risk after dimensionality reduction. Multimetal regression models showed that selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators. Multimetal RCS analyses additionally revealed a non-linear relationship of selenium with renal tubular damage risk. The BKMR models showed that the metal mixtures were positively associated with biological indicators of renal tubular damage when the metal mixtures were above the 50th percentile of concentration. Our findings indicated that natural exposure to high levels of multimetal mixtures increases the risk of renal tubular damage. Under the conditions of multimetal exposure, selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators.
先前的研究表明，接触单一有毒金属可导致肾小管损伤，而关于多金属接触对肾小管损伤影响的证据相对有限。我们旨在评估中国重金属污染农村地区成年人多金属共同暴露与肾小管损伤之间的关系。对中国重金属污染农村地区的1918名成年人进行了一项横断面研究。采用电感耦合等离子体质谱法（ICP-MS）测量参与者血浆中18种金属的水平，采用免疫比浊法测量反映肾小管损伤的敏感生物学指标（包括视黄醇结合蛋白和β2-微球蛋白）。使用最小绝对收缩和选择算子（LASSO）惩罚回归分析、逻辑回归和线性回归分析、受限立方样条（RCS）回归分析以及贝叶斯核机器回归（BKMR）方法，探讨多金属共同暴露与肾小管损伤风险或肾小管损伤指标之间的关联。降维后，血浆硒、镉、砷和铁被确定为与肾小管损伤风险相关的主要血浆金属。多金属回归模型显示，硒与肾小管损伤风险呈正相关，铁与肾小管损伤风险呈负相关或与肾小管损伤生物学指标呈负相关。多金属RCS分析还揭示了硒与肾小管损伤风险之间的非线性关系。BKMR模型显示，当金属混合物浓度高于第50百分位数时，金属混合物与肾小管损伤生物学指标呈正相关。我们的研究结果表明，自然暴露于高水平的多金属混合物会增加肾小管损伤的风险。在多金属暴露条件下，硒与肾小管损伤风险呈正相关，铁与肾小管损伤风险或其生物学指标呈负相关。
